Anticancer Effects and Cell Death Pathways in Ultralow-Power 980 nm Laser-Triggered Photodynamic Therapy by Gd₂O₃:Yb, Tm Nanoparticles

Upconverting Gd₂O₃:Yb, Tm nanoparticles that can provide photodynamic therapy (PDT) for cancer cells upon 980 nm near-infrared (NIR) laser irradiation are prepared. The nanoparticles emit bright blue upconversion fluorescence (470∼520 nm) when excited by a 980 nm laser. A well-selected PDT drug, merocyanine 540 (MC540), which shows an absorption maximum within the 495∼540 nm band, is loaded onto the surface of the nanoparticles to obtain Gd₂O₃:Yb, TmMC540. A prominent PDT-induced killing effect on both human cervical cancer cells (HeLa cells) and human hepatocellular liver carcinoma cells (HepG2 cells) is achieved under 980 nm laser irradiation at a very low power density of 0.65 W cm^–2, which is lower than The American National Standard for the safe use of 980 nm lasers (0.72 W cm^–2. The cell death modes are further studied in detail via a uranyl acetate section-staining method to analyze the morphological cell changes before and after PDT. With clear evidence of mitochondrial damage, chromatin condensation and the formation of apoptotic bodies, an apoptosis mechanism is confirmed to be responsible for both HeLa and HepG2 cell death in Gd₂O₃:Yb, Tm-MC540-mediated PDT. Due to excessive damage, the cancer cells are efficiently killed, and autophagy is found to be initiated immediately after PDT.